Efficacy and safety of lucitanib + nivolumab in patients with advanced gynecologic malignancies: Phase 2 results from the LIO-1 study (NCT04042116; ENGOT-GYN3/AGO/LIO).
Authors: Manish R. Patel, Vicky Makker, Ana Oaknin, Sandro Pignata, Floor Jenniskens Backes, Antonio Gonzalez Martin, Ramez Nassef Eskander, Bhavana Pothuri, Debra L. Richardson, Angeles Alvarez Secord, Els Van Nieuwenhuysen, Joyce F. Liu, Fernanda Musa, Richard T. Penson, Kenton Wride, Denise M. Lepley, Rachel Dusek, Teresa Cameron, Erika P. Hamilton, Nicole Concin
Journal: Journal of Clinical Oncology (2022)

5517 Background: LIO-1 is assessing the oral antiangiogenic, multikinase inhibitor lucitanib in combination with the programmed cell death receptor 1 (PD-1) inhibitor nivolumab. Individualized lucitanib dose titration is being explored to maximize lucitanib exposure and potential clinical benefit of the combination. Here, we present data from stage 1 of a Simon 2-stage design across 4 different types of advanced gynecologic cancers from the phase 2 part of LIO-1. Methods: Patients (pts) with advanced, recurrent, or metastatic endometrial cancer (EC, who received ≥1 prior platinum-based chemotherapy); cervical cancer (CC, who received ≥1 prior platinum-based chemotherapy ± bevacizumab); high-grade ovarian cancer (OC, who received ≥2 prior chemotherapies); or EC/OC with clear-cell histology (EOCC, who received ≥1 prior platinum-based chemotherapy + taxane) were enrolled. Prior PD-1 or programmed cell death ligand 1 (PD-L1) inhibitor treatment was excluded, except for up to 10 pts in the EC cohort. Pts received lucitanib at a starting dose of 6 mg once daily (QD), escalating to 8 mg QD and then 10 mg QD if safety-based titration criteria were met, plus intravenous nivolumab 480 mg every 28 days. The data cutoff was Jan 10, 2022. Results: Across cohorts, 100 pts were enrolled to stage 1; 27 (27%) remain on treatment. To date, 28 (28%) have escalated to lucitanib 8 mg, and 17 (17%) have escalated to the maximum dose of 10 mg. Confirmed responses per RECIST v1.1 have been reported in 5/22 (22.7%; 5 partial responses [PRs]) EC pts, 7/22 (31.8%; 2 complete responses [CRs], 5 PRs) CC pts, 4/33 (12.1%; 4 PRs) OC pts, and 5/23 (21.7%; 1 CR, 4 PRs) EOCC pts. Response duration ranges from 1.9+ to 13.1+ months. Of 5 pts with EC who received prior PD-1 inhibitor, there were 2 PRs, and 1 pt with ongoing stable disease of 7+ months. Grade ≥3 treatment-emergent adverse events (TEAEs) considered related to study treatment were reported in 43 (43%) pts, with hypertension the most frequent (n = 25 [25%]). Forty-six (46%) pts had a lucitanib-related TEAE that led to lucitanib interruption and 12 (12%) had one that led to lucitanib dose reduction. Eleven (11%) and 8 (8%) pts discontinued lucitanib and nivolumab, respectively, due to a treatment-related TEAE. Safety results were generally consistent across tumor cohorts. Conclusions: The combination of lucitanib + nivolumab is active in the treatment of advanced gynecological malignancies and has a manageable safety profile through effective dose titration. Stage 2 enrollment has continued in the CC cohort. Biomarker analysis is ongoing, and more mature efficacy and safety data will be presented at the meeting. Clinical trial information: NCT04042116.